METHOD OF CONTROLLING PLANT GROWTH WITH 3-SUBSTITUTED-PYRIDO {8 3,2-d{9 PYRIMIDINE-2,4-(1H,3H)-DIONES

ABSTRACT

A method for controlling plant growth and compounds used in such method. The method includes the step of applying a composition comprising substituted pyrido(3,2-d) pyrimidine-2,4(1H,3H)-diones as herein described to the locus to be protected As new compositions of matter, 3-substitutedpyrido (3,2d)pyrimidine-2,4(1H,3H)-diones, where the 3-substituent is a member of the group consisting of alkyl groups having from 2 to 8 carbon atoms, dimethoxyethyl, aralkyl groups such as benzyl, chlorosubstituted benzyl, and lower alkyl and methoxy substituted benzyl, cycloalkyl groups having from 3 to 8 carbon atoms, pyridyl substituted alkyl groups having from 1 to 2 carbon atoms, alkenyl groups having not more than 8 carbon atoms, tetrahydrofurfuryl aryl, pyrrolidino, piperidino, homopiperdino, and septamethyleneimino, and 1,3-disubstituted analogues.

lllnlte States Patent Coolre et al.

METHOD OF CONTROLLING PLANT GROWTH WITH S-SUBSTTTUTED-PYRIDO [3,2-DPYRlMlllDINE-2,4( 1H,3H )-DIONES Inventors: Anson R. Cooke, Hatboro,Pa.;

Richard L. Jacobs, Perrysburg; Ell Dee Compton, Toledo, both of OhioRelated [1.8. Application Data Division of Ser. No. 832,026, June 10,1969, Pat. No.

3,752,816, which is a continuation-in-part of Ser. No.

740,047, June 26, 1968, abandoned, which is a continuation-in-part ofSer. No. 740,089, June 26, 1968, abandoned.

US. Cl 71/92, 71/66, 71/74 lnt. Cl A01n 9/22 Field of Search 71/92References Cited UNITED STATES PATENTS 1/1972 Jacobs 7l/92 PrimaryExaminer-James 0. Thomas, Jr. Attorney, Agent, or FirmErnest (G. Szoke;Michael E. Zall [5 7 ABSTRACT A method for controlling plant growth andcompounds used in such method. The method includes the step of applyinga composition comprising substitutedpyrido[3,2-d]pyrimidine-2,4(lH,3IH)-diones as herein described to thelocus to be protected As new compositions of matter, 3-substitutedpyrido[3,2-d]pyrimidine-2,4(lH,3H)-diones, where the 3-substituent is a memberof the group consisting of alkyl groups having from 2 to 8 carbon atoms,dimethoxyethyl, aralkyl groups such as benzyl, chlorosubstituted benzyl,and lower alkyl and methoxy substituted benzyl, cycloalkyl groups havingfrom 3 to 8 carbon atoms, pyridyl substituted alkyl groups having from ito 2 carbon atoms, alkenyl groups having not more than 8 carbon atoms,tstrebzs r fertury aryl, p q i ine ..P iPE F homopiperdino, andseptame'thyleneimino, and

1,3-disubstituted analogues.

12 Claims, No Drawings METHOD OF CONTROLLING PLANT GROWTH WITH3-SUBSTITUTED-PYRIDO [3,2-lD] PYRIMIDINE-2,4-(1H, 3H)-DIONES This is adivisional of Ser. No. 832,026, now US. Pat. No. 3,752,816, filed June10, 1969, which is a continuation-in-part of applications Ser. No.740,047 and Ser. No. 740,089, both filed June 26, 1968 and both nowabandoned.

BACKGROUND OF THE INVENTION This invention relates to a method forcontrolling plant growth, and to new compounds used in such method whichhave been found to have utility as plant growth regulators, totalherbicides, selective weed killers, and defoliating agents.

In recent years increased crop yields have been made possible by thedevelopment and use of chemicals which are specifically toxic to weeds,yet do not damage crops around which they are applied. In general, thecurrently available chemicals which are most desired for theirselectivity and as total herbicides are sufficiently expensive thatexpense is a significant factor in their use. Therefore, new compoundsand inexpen sive methods for producing such compounds are constantlybeing sought.

In addition, while many compounds presently on the market are effectiveto control the growth of certain species of weeds, they are ineffectiveagainst others. Thus new herbicides which have broad spectrum effectiveness against a wide variety of weeds are continually being sought. Afamily of compounds which has been found particularly effective issubstituted pyrido[3,2- d]pyrimidine-2,4(1H,3H)-diones of the typedescribed herein.

An object of the invention is a method for controlling weeds.

Another object of the invention is the provision of a new family ofcompounds useful as broad spectrum herbicides.

Other objects and advantages of this invention will be apparent from thedescription to follow:

SUMMARY OF THE INVENTION The compositions of the invention comprisecompounds of the formula I" N 7 f (|3=() lie 4 3N-R xy wherein R and Rare always dissimilar, wherein R is a member of the group consisting ofalkyl groups having from 2 to 8 carbon atoms, dimethoxyethyl, aralkylgroups where the alkyl portion has from I to 2 carbon atoms and thearomatic portion is phenyl or a substituted phenyl having 1 or 2 methyl,methoxy or chlorine substituents on the benzene ring, cycloalkyl groupshaving from 3 to 8 carbon atoms, pyridyl substituted alkyl groups havingfrom 1 to 2 carbon atoms, alkenyl groups having not more than 8 carbonatoms, tetrahydrofurfuryl, pyrrolidino, piperidino, homopiperidino,septamethyleneimino, and phenyl, and wherein R is hydrogen or a loweralkyl group having from I to 4 carbon atoms. These compounds are namedas 3- 2 substituted-pyrido[ 3,2-d]pyrimi-dine-2,4( 1H,3H)- diones, andl,3-disubstituted-pyrido [3 ,2- d]pyrimidine-2,4(1H,3H)-diones.

The method of the invention comprises applying an effective quantity ofat least one of the above compounds to the locus to be protected.

Most of the 3-substituted-pyrido[3,2-d]pyrimidine- 2,4(1H,3H)diones ofthe invention can be produced by reacting (l) a compound having theformula wherein R is a member of the group consisting of alkyl groupshaving from 2 to 8 carbon atoms, dimethoxyethyl, aralkyl groups wherethe alkyl portion has from 1 to 2 carbon atoms and the aromatic portionis phenyl or a substituted phenyl having 1 or 2 methyl, methoxy orchlorine substituents on the benzene ring, cycloalkyl groups having from3 to 8 carbon atoms, pyridyl substituted alkyl groups having from 1 to 2carbon atoms, alkenyl groups having not more than 8 carbon atoms, andtetrahydro-furfuryl, with (2) sodium hypochlorite, the reaction beingcarried out in the presence of sodium hydroxide and a suitable solvent,preferably at elevated temperatures.

The reaction is illustrated generally below, R having the meaningassigned in explaining the immediately absence of heat, but isaccelerated by heating the reaction mixture. For that reason it ispreferable to heat the 1) NaOCl N H reaction mixture to a temperaturefrom about 50* tothe boiling temperature thereof, most desirably about6080, and hold it at such temperature for about /2 hour. Thereafter themixture is cooled to room temperature and neutralized with acid at whichtime the reaction product precipitates. *All temperatures reportedherein and in the attached claims are in degrees centigrade unless otherspecified.

The corresponding 1,3-disubstituted compounds can be produced byalkylating the 3-substitutedpyrido[3,2-d] pyrimidine-2,4(lH,3H)-dionesproduced as above; this can be done by reacting the dione with an alkylhalide in the presence of sodium hydride and a solvent such astetrahydro-furan, dimethylformamide or dimethylsulfoxide.

This invention can be more clearly understood by reference to thefollowing examples. The examples, however, are not intended to belimitative.

EXAMPLE I Preparation of 3-SEC-Butyl-Pyrido[3,2-d] Pyrimidine-2,4(lH,3H)-Dione A 22 l. flask equipped with a stirrer and a thermometer,and surrounded by a heating mantle was charged with 6 1. water, 369 g.sodium hydroxide and 11.65 1. aqueous solution containing 745 g. NaOCl.Stirring was commenced, and was continued throughout the reaction. Whenthis charging was complete, the temperature of the charge was 34; then2.2 Kg. N -sec-butyl- 2,3-pyridinedicarboxamide was added to the NaOCl-NaOH solution in the flask. After the pyridinedicarboxamide dissolved,the temperature of the reaction mixture was 33; the reaction mixture wasthen heated for a total of about 50 minutes. The temperature afterminutes of heating was 60, after minutes of heating 67. The heatingmantle was then removed, and the flask was immersed in an ice bath forabout 1 hour 45 ture of the charge was 31; then 1.76 Kg. N -isopropyl-2,3-pyridine-dicarboxamide was added to the NaOCl- NaOH solution in theflask. After the pyridinedicarboxamide dissolved, the temperature of thereaction mixture was 33; the reaction mixture was then heated for atotal of about minutes. The temperature after 10 minutes of heating was40, after 15 minutes 44, after 21 minutes 52, after 25 minutes and after55 minutes 63. The heating mantle was then removed, and

10 the flask was immersed in an ice bath for about 2 hours 50 minutes;the final temperature of the reaction product was 10. The reactionmixture was then acidified by making a gradual addition of glacialacetic acid to a pH of 6. The rate of addition of acetic acid wascontrolled minutes; the final temperature of the reaction product 15 sothat the temperature of the reaction mixture in the was 17.Approximately a liter receiving vessel was then charged with 600 ml.glacial acetic acid, and immersed in an ice bath. The reaction productwas then added gradually to the acetic acid in the receiver, withstirring. The rate of addition of the reaction product was controlled sothat the temperature of the liquid in the receiver remained within therange of 10 to 15. The pH of the liquid in the receiver was monitored,and additions of glacial acetic acid were made, as required, to preventthe pH thereof from rising above about 6. The3-sec-butyl-pyrido[3,2-d]pyrimidine-2,4(111,311)- dione product, whichhad separated as an off-white to cream precipitate, was separated fromthe mother 1iquor by filtration, using a Buchner funnel. The finalproduct was washed with tap water and dried in a circulating air oven inwhich the air was maintained at a temperature within the range of to100. The total recovery of dried product amounted to 2.45 Kg, or percentof theory. It was determined by nuclear magnetic resonance analysis thatthe product was 87 percent, plus or minus 4 percent,3-sec-butyl-pyrido[3,2- d] pyrimidine-2,4(1H,3H)-dione. The remainder ofthe product was 3-sec-butyl-pyrido[2,3-d]pyrimidine- 2,4(1H,3H)-dione.The presence of the [2,3-d]-family compound, is attributable to animpurity in the amide starting material.

EXAMPLE 11 Preparation of 3-1sopropyl-Pyrido[3,2-d] Pyrimidine-2,4(lH,3H)-Dione A 22 l. flask equipped with a stirrer and a thermometer,and surrounded by a heating mantle was charged with 8 1. water, 398 g.sodium hydroxide and 9.5 1. aqueous solution containing 595 g. NaOCl.Stirring was commenced, and was continued throughout the reaction. Whenthis charging was complete, the temperaflask remained within the rangeof 10 to 15. The 3- isopropyl-pyrido[ 3 ,2-d]pyrimidine-2,4(ll-l,3H)-dione product, which had separated as an off-white to creamprecipitate, was separated from the mother liquor by 20 filtration,using a Buchner funnel. The final product was washed with tap water anddried in a circulating air oven in which the air was maintained at atemperature within the range of 80 to The total recovery of dry product,melting point 25 238244, amounted to 1.48 Kg, or 89.8 percent of theory.It was determined by nuclear magnetic resonance analysis that theproduct was 98 percent, plus or minus 2 percent,3-isopropyl-pyrido[3,2-d]pyrimidine- 2,4(lH,3l-l)-dione. The remainderof the product, if

was 3-isopropyl-pyrido[2,3-d] pyrimidine- 2,4(1H,3H)-dione. The presenceof the [2,3-d]-family compound, if any, is attributable to an impurityin the amide starting material.

It will be noted that, in the procedure described in 35 Example I, thereaction product was added to glacial acetic acid while, in theprocedure described in Example ll, glacial acetic acis was added to thereaction product. It has been found that, in some instances, the Example11 procedure causes the dione product to ap- 40 pear as a sticky solid;this causes difficulty in workup. Such difficulty is minimized, oreliminated altogether when the Example 1 technique is used; thisprocedure is, therefore, preferred.

45 EXAMPLES lII THROUGH xxv Numerous other compounds of the inventionhave been produced by the above described method. Information concerningstarting materials, batch sizes, final product and yield forrepresentative ones of such preparations is presented in Table 1, below:

TABLE I Starting Amide Metal Hypohalite Base Name or m Name or Addedwater.

Example Name grams formula grams Solution formula grams ml.

111 N -cyclohexyl- 1985 NaOCl 580 9500 NaOH 396 8,000

2,3-pyridine dicarboxamide IV N cthyl-2,3- l0 NaOCl 3.9 50.2 NaOH 2.0625 pyridine dicarboxamide V N -propyl-2,3- 41.4 NaOCl 14.9 192 NaOH 8.3300 yndme dicarboxamidc V1 N-allyl-2,3- 30.8 NaOCl 11.2 146 NuOH 6.1 230pyridine dicarboxamidc TABLE II-Contlnued Example Time TemperatureMinutes-Seconds XVIII :00 12 9:00 15 37:00 35 49:00 50 65:00 70 89:00 69XIX 0:00 16 :00 19 15:00 42 25:00 60 35:00 68 45:00 70 50:00 57 XXI 0:0012 25:00 14 50:00 19 85:00 22 145:00 58 165:00 73 190:00 70 205:00 40XXII 0:00 17 7:00 30 22:00 63 27:00 66 52:00 62 XXIII 0:00 2:00 :00 5035:00 70 40:00 65 XXIV 0:00 15 1:00 20 5:00 15:00 45 18:00 50 28:00 7030:00 72 :00 70 50100 60 XXV 0:00 15 5100 20 15:00 18:00 50 23:00 6030:00 70 50:00 62 The structures of the final compounds of Examples 111through XXV were confirmed by elemental analysis, and by infrared andnuclear magnetic resonance spectra.

The production of 3-substituted-pyrido[3,2-d]pyrimidine-2,4(lH,3H)-diones of this invention where the 3-substituentis an alkyleneimine or aryl is discussed subsequently herein. The other3-substituted pyrido[3,2-d]pyrimidine-2,4( lH,3H)-diones of thisinvention can be made by the procedures described in Examples I and 11,above. substituting the appropriate dicarboxamide for the N-sec-butyl,2,3-

pyridinedicarboxamide and the N' -isopropyl-2,3- pyridinedicarboxamidestarting materials.

EXAMPLE XXVI Preparation of 3-Isopropyll -Methyl-Pyrido[ 3,2-d]Pyrimidine- 2,4( lH,3H)-Dio:ne

A 250 ml. 3-necked flask partially immersed in an ice bath and equippedwith a stirrer, condenser, thermometer, addition funnel, gas inlet andoutlet tubes, and nitrogen atmosphere system was assembled. The nitrogenwas turned on, and 1.3 g. NaH (washed in petroleum ether) and 50 ml.dimethylformamide was charged into the flask. Agitation was begun andcontinued throughout the reaction. The temperature at this point was 25.20 minutes later the temperature had fallen to 18. At this time thenitrogen was turned off, and the addition of 10.3 g. 2,4(1I-I,3H)-dionedissolved in 1 10 ml. of dimethyl- I forrnamide, was begun. A light grayslurry began to form, turning to brown during the 20 minutes it took tocomplete the charging of the dione. After completion of the charging ofthe dione, 2.5 g. CH Cl was introduced into the reaction mixture at therate of 0.5 g. per minute. A hazy light brown solution formed turning toreddish brown as the addition progressed. The temperature at this pointwas 21. Another 2.5 g. of CI-I CI was then charged at the rate of 0.5g./minute. Solids precipitated, forming a red orange colored slurry. Thetemperature at this point was 26 and the pH was between 8 and 9. Theslurry was stirred for an additional 3 hours. The total elapsed time atthis point was 9 hours.

The slurry was set aside overnight. Then it was quenched into 1,120 ml.of tap water (a 7 to 1 ratio of water to dimethylformamide) forming aclear light tan solution. The solution was stirred for 1 hour, then thepH was adjusted to 5 with dilute hydrochloric acid. No solids wereapparent. Then the solution was partially evaporated and the precipitatefiltered and dried. The filtrate was evaporated still more and a secondcrop filtered and dried.

The total yield was 10.1 g. or 91.8 percent of theory. Infrared analysiswas in agreement with the structure for 3-isopropyl' l -methyl-pyrido[ 3,2-d]pyrimidine- 2,4( ll-I,3H)-dione.

The other l,3-disubstituted-pyrido[ 3 ,2- d]pyrimidine-2,4(1H,3H)-di0nesof this invention can be made by the procedure described in Example XXVIabove, substituting the appropriate alkylating agent or3-substituted-pyrido[3,2-d]pyrimidine-2,4( 111,311)- dione for thestarting materials used therein.

DISCUSSION OF THE REACTANTS The best yields are obtained when oneequivalent of base and one equivalent of hypohalite are used for eachmole of the amide. Satisfactory results, however, have been achievedwhen as much as two equivalents of the hypohalite were used per mole ofthe amide.

While the method above described contemplates the use of alkali andalkaline earth metal hydroxides and alkali and alkaline earth metalhypohalites, sodium hydroxide and sodium hypohalite are preferred foreconomic reasons only. The other metal hydroxides and metal hypohalitesare perfectly satisfactory but the cost thereof is much greater.

3-isopropyl-pyrido[3,2-d1pyrimidine- The metal hypohalite may beprepared by reacting chlorine or bromine with a water solution of analkali metal or alkaline earth metal hydroxide, preferably so diumhydroxide. For example, a l N. sodium hypochlorite solution can beprepared by reacting 79.98 g. NaCH with 70.9 g. chlorine (C1 insufficient water to make one liter. It can be appreciated that oneequivalent of bromine (Br can be substituted for chlorine to produce asodium hypobromite solution; and in the same manner, 1 equivalent of analkali or alkaline earth metal hydroxide can be substituted for thesodium hydroxide to produce a different metal hypohalite.

Water is the preferred solvent medium for the reaction for economicreasons. Other solvents could be used alone or mixed with water if theydid not interfere with the course of the reaction or react with thefinal products. The exact amount of water or other solvent to be used isnot critical.

DISCUSSION OF THE REACTION METHOD In carrying out the process describedin Example I or Example II for producing the compositions of theinvention the metal hypohalite should first be admixed with the base,and then the amide should be added thereto. If the components are notadmixed in this manner, there is a tendency for the amide to hydrolyzeto the corresponding acid resulting in a lower yield.

The temperature at which the reaction is conducted can range from to 100with 60,80 being the most preferred. The reaction mixture should be heldat the desired temperature for about /2 hour or until a negative testfor hypohalite indicates the completion of the reaction.

At the end of the reaction, the reaction mixture is cooled to roomtemperature and neutralized with acid to a pH in the range of to 4 toprecipitate the product which can then be collected by filtration,washed and dried. The preferred pH range is from 5 to 6. Any acid can beused for the pH adjustment but mineral acids and simple organic acidssuch as acetic acid are most preferred for economic reasons.

The N-substituted 2,3-pyridinedicarboxamides which constitute a familyof starting materials in producing the compounds of this invention canbe made from corresponding 2,3-pyridinedicarboxylic acid according tothe method described in Example A below. The preparation of N-isopropyl-2,3-pyridinedicarboxamide is used as an example.

EXAMPLE A A 2-liter, 3-necked flask equipped with a stirrer and athermometer, and partially immersed in an oil bath was charged with 400g. 2,3-pyridinedicarboxylic acid, 400 g. acetamide, and 400 ml. aceticanhydride. Agitation was begun and continued throughout the reaction.The reaction mixture was then heated rapidly to a temperature of 136 andheld at that temperature for 2 hours. During this period the acetic acidwhich was produced was distilled off. At the end of this time, themixture was cooled, the solids removed by filtration, and the filtrateset aside. The solids were washed with cold methanol, dried, andweighed. The yield was 251.6 g. light tan material having a meltingpoint of 239-240. The filtrate which had been set aside was concentratedin vacuo, and a precipitate of 9.2 g. medium brown material having amelting point of 239240 was recovered by filtration. The total yield was260.8 g. 2,3-pyridinedicarboximide. The 2,3- pyridinedicarboximide wasused to prepare N isopropyl-Z.3-pyridinedicarboxamide, in the followingmanner.

A 500 ml. flask equipped with a stirrer, condenser. thermometer,bubbler, and addition funnel, and partially immersed in an ice bath, wascharged with 29.6 g. 2,3-pyridinedicarboximide and ml. 2-propanol.Agitation of the flask contents was begun and continued throughout theduration of the reaction. An addition of 11.8 g. isopropylamine was thencommenced and charged over a 2 minute period. After the charging, thereaction mixture was stirred for an additional 2 hours and 10 minutes,during which time the temperature of the reaction mixture reached a highof 34. At the end of this time, the thick slurry which had formed wascooled to about 3, the solids were removed by filtration, and thefiltrate was set aside. The solids were then washed with cold 2-propanoland dried. The yield was 33.8 g. product which had a melting point ofl39140, and was identified by Infrared Spectroscopy as N-isopropyl-2,3-pyridinedicarboxamide.

The other amide starting materials used to produce the compositions ofthis invention can be made in substantially the same manner,substituting the required amine for the isopropylamine employed in theforegoing procedure. In some instances a mixture of isomers is produced.If so, separation can be accomplished either by preferentialprecipitation or by column chromatography. Not all of the compounds ofthis invention can be prepared in the manner described in ExamplesI-XXV. For example, 3-substituted-pyrido[3,2- d]pyrimidine-2,4(lH,3H)-diones where the 3- substituent is an aryl group or analkyleneimino group cannot be produced in the aforedescribed manner, sofar as is known. They can be produced by other methods, however. Thealkyleneimino substituted compounds can be produced by the reactionsillustrated becarboethoxy-B-pyridyDurea 3-piperidino-pyrido[3, 2-d]pyrimidine-2, 4 (1H, 3H)-dl0uu *The symbol N S is used herein, and inthe appended claims, to mean N CHLVCHZ The following example illustratesthe preparation of 3-piperidino-pyrido[3,2-d]pyrimidine-2,4( 1H,3H)-dione.

EXAMPLE XXVII Preparation of3-Piperidino-Pyrido[3,2-d]Pyrimidine-2,4(1H,3H)- Dione Preparation ofEthyl 3-Aminopicolinate Ethyl-3-aminopicolinate was produced from 49 g.3- aminopicolinic acid and 80 ml. sulfuric acid* dissolved in 200 m1.anhydrous ethanol. The reagents were combined and heated under refluxfor 16 hours; and the reaction mixture was then poured onto 3 l. crushedice and neutralized with solid potassium bicarbonate. A solidprecipitate which formed was separated from the water-ethanol-sulfuricacid phase by filtration, and was extracted with 200 ml. hot acetone.The water-ethanolsulfuric acid fraction was extracted 6 times with 100ml. portions of methylene chloride. The methylene chloride and acetoneextracts were combined, dried with anhydrous magnesium sulfate, andconcentrated under reduced pressure. Evaporation of the methylenechloride and acetone to leave a volume of about 50 ml. reaction mixturecaused precipitation of solids which were recovered by'filtration,recrystallized from 300 ml. benzene and identified by infraredspectroscopy as ethyl 3-aminopico1inate, melting point 126l29. Found andcalculated elemental analyses for another batch of ethyl3-aminopicolinate, which batch was found by infrared spectroscopy andmelting point to be identical with that described above, were asfollows: *98 percent. by weight Theory Found C 57.82% 57.87% H 6.07%6.19% N 16.86% 16.89%

Preparation of Ethyl 3-Isocyanatopicolinate Ethyl 3-isocyanatopicolinatewas produced from 3.3 g. ethyl 3-aminopico1inate and phosgene. The ethyl3- aminopicolinate produced as described above was first dissolved intoluene, and the resulting solution was saturated, with stirring, withdry hydrogen chloride gas. About a 13 temperature rise indicated theoccurrence of an exothermic reaction. After about 2 hours a whitishprecipitate which was the hydrochloride of ethyl 3- aminopicolinatebegan to appear. Reaction was continued, with stirring, for a total ofapproximately 8 hours. The toluene slurry was heated, under reflux, andsaturated rapidly with an excess of phosgene. Phosgenation was continuedfor a total of 6 hours, during which time the reaction mixture was keptsaturated with phosgene. After phosgenation, the toluene solvent wasdistilled from the reaction mixture, leaving a tan oil which wasidentified by infrared spectroscopy, by nuclear magnetic resonance, andby elemental analysis, as {ethyl 3- isocyanatopicolinate. Preparation of1-Piperidino-3( 2carboethoxy-3-pyridyl) urea The ethyl3-isocyanatopicolinate produced as described above was dissolved in 50ml. benzene and approximately a 4 g. portion of N-aminopiperidine wasadded dropwise to the resulting solution. A slight temperature riseindicated exothermic reaction. The reaction mixture was refluxed for 4hours and was then acidified with acetic acid until a white precipitateformed. The white product, melting point l82-l83, was identified byinfrared spectroscopy as l-piperidino- 3-(2-carboethoxy-3-pyridyl) urea.Preparation of 3-Piperidino-pyrido[3,2-d]Pyrimidine-2,4(ll'1,3l-l)-Dione The l-piperidino-3-(2-carboethoxy-3-pyridyl) ureaproduced as described above was dissolved in 40 ml. solution of equalparts by volume of 37 percent hydrochloric acid and ethyl alcohol andheated under reflux for 5 hours. The solvent was then evaporated,leaving a brown oil, which was allowed to stand overnight, during whichstanding a solid precipitated,0.3 g., melting point 265270. The solidwas identified by infrared spectroscopy as the hydrochloride salt of3-piperidinopyrido[3,2-d]pyrimidine-2,4(1l-1,3H)-dione. Thebydrochloride salt was dissolved in. water acidifiedwith hydrochloricacid to a pH of 2, and the resulting solution was neutralized to a pH of8 with potassium bicarbonate to cause reprecipitation of the finalproduct, melting point 290300, identified by infrared spectroscopy as3-piperidino-pyrido[3,2-d]pyrimidine- 2,4(lH,3H)-dione. Afterrecrystallization from ethyl alcohol, the final product had a meltingpoint of 301-303, and was white and crystalline. The elemental analysisand theory, for purposes of comparison, were as follows:

Theory Found C 58.53% 58.36% H 5.73% 5.83% N 22.75% 22.55%

The other 3-methyleneimino-pyrido[3,2-

3-phonyl-pyridol3, 241] pyrimidine-2, M111, 5111)- dlonc 15 Thefollowing example illustrates the production of3-phenyl-pyrido[3,2-d]pyrimidine-2,4( lH,3H)-dione by reaction betweenphenylurea and ethyl 3- aminopicolinate.

EXAMPLE XXVIII 3-phenyl-pyrido[3,2-d]pyrimidine-2,4(1H,3I-I)- dione wasproduced from 8.3 g. ethyl 3- Time Temperature At the end of the 1 hourminute heating period, the beaker contained a finely divided solid, andheating was discontinued. The crude product from this reaction, 8.8 g.,was combined with crude 3-phenylpyrido[3,2-d]pyrimidine-2,4(lH,3H)-dione. from other batches to provide a total of 17.3 g. crude.This mate rial was dissolved in 150 ml. dimethyl sulfoxide at 100,carbon treated and quenched into 1 1. water; tan colored solids whichprecipitated were recovered by filtration, and identified by infraredspectroscopy as 3- phenyl-pyrido[3,2-d]pyrimidine-2,4( lH,3I-I)-dione.The yield was 14.4 g. purified product.

Other 3-aryl-substituted-pyrido[3,2-d]pyrimidine- 2,4( lI-I,3H)-dionescan be produced by the procedure described above in Example XXVIII,merely by substituting for the phenylurea an equivalent amount of theappropriate aryl urea. Examples of known aryl ureas which can be so usedinclude m-tolylurea, o-tolylurea, 5-chloro-o-tolylurea and p-tolylurea.

Reaction between the 3-aminopicolinic acid and phenyl isocyanate hasalso been utilized to produce 3- phenyl-pyrido[3,2-d]pyrimidine-2,4(lH,3H)-dione. The reaction proceeds readily if the phenyl isocyanate andthe 3-aminopicolinic acid are merely heated under reflux, and isillustrated by the following example.

EXAMPLE XXIX Preparation of3-Phenyl-pyrido[3,2-d]Pyrimidine-2,4(1l-I,3H)-Dione Reaction between 12g. phenyl isocyanate and 7 g. 3-aminopicolinic acid was utilized toproduce 3- phenyl-pyridol3,2-d]pyrimidine-2,4(1H,3H)-dione. The3-aminopicolinic acid and the phenyl isocyanate were merely charged toan appropriate vessel, and heated under reflux for 1 hour. The reactionmixture was then cooled to 100C; a charge of 150 ml. 5 percent sodiumhydroxide solution was then added to the reaction mixture; and theresulting mixture was stirred at a temperature of about C. forapproximately 1 hour and then cooled to room temperature. An addition ofml. 10 percent sodium hydroxide solution was then made; the mixture washeated to 90; and insoluble material was separated from the solution byfiltration. The filtrate was acidified to a pH of 5.6 with acetic acid.Insoluble material, approximately 1 /2 g., was separated from the liquidby filtration, and recrystallized from methyl alcohol. Therecrystallized material, 0.5 g., melting point in excess of 330, waswhite in color and was identified by infrared spectroscopy as3-phenyl-pyrido[3,2-d]pyrimidine-2,3( lH,3H)-dione.

The procedure described above in Example XXIX can also be used toproduce other3-aryl-substitutedpyrido[3,2-d]pyrimidine-2,4(lH,3H)-diones, merely bysubstituting an equivalent amount of the appropriate isocyanate for thephenyl isocyanate used in the Example XXIX procedure. Examples of otheraryl isocyanates which can be so substituted include: o-tolylisocyanate, p-tolyl isocyanate, m-tolyl isocyanate, pfluorophenylisocyanate, a-naphthyl isocyanate, pnitrophenyl isocyanate,m-nitrophenyl isocyanate, onitrophenyl isocyanate, p-chlorophenylisocyanate, mchlorophenyl isocyanate, o-chlorophenyl isocyanate,p-bromophenyl isocyanate.

The substituted pyrido[3,2-d]pyrimidine- 2,4( lH,3H)-dione compoundshave been found to display unexpectedly high levels of herbicidalactivity and to be useful in controlling undesirable plants of both themonocotyledonous and the dicotyledonous species on either apostemergence or a preemergence base.

By preemergence is meant that the compound is applied to the soil priorto emergence of the weed species sought to be controlled. This term, asused herein, also means the application of the herbicidal compoundsfalling within the scope of this disclosure to areas wherein useful ordesirable plants are either growing or have been sown, but where theundesirable plants sought to be controlled have not as yet emerged.

By the term postemergence is meant that the compound is applied to theplant sought to be controlled after it has emerged from the soilsurface. This term is also used to describe the application ofherbicidally active compounds to soil surface in and around growingplants sought to be controlled for purposes of effecting root absorptionby the undesirable plant species.

Especially active are the compounds where the lsubstituent is hydrogenand the 3-substituent is isopropyl, butyl, sec-butyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclooctyl, piperidino or benzyl, and thel-methyl analogues.

The method of the invention will be more clearly understood by referenceto the following examples.

EXAMPLE XXX The preemergence and postemeregence herbicidal activity of3-isopropyl-pyrido[3,2-dlpyrimidine- 2,4(1I-I,3l-I)-dione achieved atvarious application rates is shown in Table III below.

In using the compound, seeds of the type of plants set forth in TableIII were sown in fresh soil. In the preemergence test the soil wassprayed with a solution of the test compound immediately after the seedswere planted, and before any noticeable growth developed in the testarea. The solution was about a 2 percent by weight solution of thecompound in acetone and/or alcohol. The compound was applied at the rateof 16 pounds per acre of soil surface.

Approximately 3 weeks after spray application, the herbicidal activityof the compound was determined by The same solutions of the samecompound can also be sprayed,'for example along railroad right-of-ways,at an application rate of about 2 to 16 pounds per acre as a totalherbicide, i.e., to prevent all vegetation. The

visual observation of the treated area in comparison 5 other compoundsdisclosed herein can be used as prewith untreated control areas. Theseobservations are emergence or postemergence herbicidesin a similarreported below in Table III wherein the average activity manner. In thecase of 3-cyclohexyl-pyrido[3,2 rating is reported as the percentcontrol of plant d]pyrimidine-2,4(1H,3H)-dione and 3-sec-butylgrowth.pyrido[3,2-d]pyrimidine-2,4(1H,3H)-dione, substan- In the postemergencetest the soil and developing tially the same application rates, e.g., assimilar or salt plants were sprayed about two weeks after the seedssolutions in water, are effective; this is also generally were sown. Thecompound was applied at the rate of true of the other members of thepyrido [3,2- 8 pounds per acre from about a 2 percent by weightsod]pyrimidine-2,4( lH,3 y, a1th0ugh lution of the test compound inalcohol and/or acetone. slightly higher application rates may berequired. 3- The postemergence herbicidal activity was measured in y pyl ]py 0 the same way as the preemergence activity; i.e., visual has beenfound to be peculiarly effective because of its observationapproximately 1 1 days after spraying, and selectivity; for example,applied as described above, at expressed as the percent control of plantgrowth. an application rate of 16 pounds per acre, the benayl TABLE IIIcompound showed no preemergence herbicidal activity 20 againstcucumbers, corn, or snapbeans, but total pre- Compound Applied:3-isopropyl-pyrido[3,2-dI emergence activity against alfalfa,cheatgrass, crab- P K fi lgrass, curled dock, chickweed, pigweed andlamb- Preemergence Postemergence squatters- Treatment Treatment Control7! Control Alfalfa 100 I00 Corn 100 100 Wild Oats 100 100 Informationconcerning the substituted pyrido [3,2- g fld]pyrimidine-2,4(lH,3H)-dione family of compounds OXldll I00 100gamymdgmss 100 100 applled as described, and dlscussed above as havlngan Cwbgwss 100 100 unexpectedly high order of herbicidal activity, ispresiggggfi {3g 3g ented in the following Table IV below. In Table IV,the Curlcd Dock so 100 entries under Pre" refer to a preemergence testand ilm j gg igg :88 those under Post" refer to a postemergence test.All Chickwced 100 100 test results are at application rates of 8 poundsper acre Cucumber 100 100 except those of certain preemergence testing(16 sfngag g8 {88 pounds per acre or as otherwise indicated) asindicated Lambsquarters 100 100 by an asterisk following Pre": Pre*".

TABLE IV Compound Applied Percent control 3 propylpyrimidinc- [3,2-d]pyrido[3,2-d] pyrillo[3,2-d] pyrido[3,2-d] pyrido[3,2-d] pyrido[3,2-d]2,4(1IL3H) pyrinlidincpyrimidine pyrimidinepyrimidincpyrimidiucpyrimidinedione 2,4(1H,3H)- 2,4(1H,3H)- 2,4(1H,3H)-2,4(1H,3H)- 2,4(1H,3H)- 2,4(1H,3H)- (control) dione dione dione dionedione diono Pre* Post Pre" Post Pic" Post Pro Post Pro" Post Pro* PostPre" Post 0 0 100 50 100 100 100 50 100 100 100 100 0 O l) 0 10 10 10060 100 50 100 90 50 3O 0 0 0 0 100 0 100 90 100 100 100 100 100 20 O 0 00 100 30 100 100 100 100 100 100 100 30 0 0 0 0 40 100 100 100 100 100100 90 100 0 0 0 0 40 10 100 100 100 100 100 100 90 100 0 0 0 0 100 80100 100 90 100 100 100 100 100 10 10 i) 0 10 10 20 70 100 90 100 100 2030 0 0 Johnsongras 0 0 60 60 100 100 100 100 100 100 90 100 0 0 Curleddock- 0 O 100 90 100 100 90 100 100 100 100 100 0 10 Snapbeans O 0 10080 100 100 100 100 100 100 100 100 0 0 Yellow rocket 0 0 100 100 100 100100 90 100 100 100 100 90 U0 Chickweed- 0 0 100 100 100 100 100 100 100100 100 100 70 Cucumber- 0 0 100 50 100 100 100 100 100 100 100 100 1020 Pigweedt 0 O 100 90 100 100 100 90 100 100 100 100 O 100 VclvcrtleatA (l 0 90 100 100 100 100 100 100 100 90 1.00 0 0 Lambsq uarters 0 0 100100 100 100 70 10 100 100 100 100 30 100 Percent control 3 cyclopropyl 3cyclohexyl 3-cyclooctyl- 1,3-dimcthyll-methylJi-isopro- B-benzyl pyridopyrido[3,2-d] pyrido[3.2 d] pyrid0[3,2-d] pyrido[3,2d] pyl-pyrido[3,2-d][3,2-(11 pyrimidiucpyrirnidillepyrimidinepyrimidinepyrimidlncpyrimidine-2.4(1H,3II) 2,4(11'L3ID- 2,4(1H,3H)- 2,l(1lI,3II)- l,-l(llL3lI)-.Z,-t(1H,3lI)- (iiono lliollll diollc diullv lllOllt lliollc Pro lostlrv Post lrc" lost lrll* Post lrv. lost lrv Post Alfalfa 100 0 100 30100 0 0 100 100 0 Corn... 10 0 90 40 50 0 (l U l] t) 10 0 Wild oats G0100 100 100 10 (l l) ltil) 2U 30 I] Cllealgl as 100 U 100 80 100 30 t)l) 101) 40 100 0 Foxtail 10 0 100 100 100 80 0 0 20 40 iii) 0Bllrnyardgmss 10 l] 100 100 lit] 0 0 '10 0 ill) (I [3,2411pyrirnidine-[3,2-d

eth l)]-pyrido l pyrimidinc- [3,2-dizgoyrimidine- TAB LE IV ContinuedPercent control 3 cyclopropyl 3 cyclohcxyl S-cyclooctyl- 1,3-dimethyl1-methyl-3-isopro- 3-benzyl pyrido pyr1 d0[3, 2-d] pyn do[3, 2-d] pyrido[3,2-d] pyrido[3,2-d] pyl-pyrido[3,2-d] [3,2-(11 pyrimidinepyrimidinepynmidincpyrimidincpyrimidine pyrimidine- 2,4(1 H,3H)- 2,4(1H,3H)- 2,4(1H,3H)- 2,4(1H,3H)- 2,4(l[-I,3H)- 2,4(1H,3H)- drone dronedione dionc dionc dione Pre" Post Pre Post Pre Post Pre" Post Pro PostPre Post Crabgrass 100 10 100 100 100 100 10 50 0 100 40 Nutgrass O 0100 100 20 0 0 0 0 0 0 Johnsongrass. 10 0 100 100 100 100 O 0 30 0 90 0Curled dock. 100 10 100 100 100 100 30 0 80 100 100 0 Sna bean. 100 0100 80 100 90 0 100 100 10 0 Yel ow rocket 100 100 100 100 100 100 0 0100 100 90 70 Ch1ckwecd 100 100 100 100 100 100 0 0 100 90 100 100Cncnmber. 100 20 100 100 90 100 0 0 100 103 0 l0 Prgweed- 100 90 100 100100 O 0 100 100 100 100 VelvetleaL. 100 0 100 100 100 100 0 0 100 100 90Lambsquarters 100 100 100 100 100 100 10 0 100 100 100 60 "Presented forpurposes of comparison, and not in accordance with the invention.

Percent control 3-cyc lopcntyl- 3-cyclohcpty1 3-a-phenethyl-3-(2,2-dimethpyr1d o[3,2-d] pyrido[3,2-d] pyrido[3,2 d] oxyethyD-pyridopynm1dinc-2,4 pyrimidine-2,4 pyrimidine-2,4 [3, 2-d] (1H,3H)-dione(1H,3H)-dione (1H,3H)-dione pyrimidine-2,4 (1H,3H)-dione Pre Post PrePost Pre Post Pre Post Corn 100 80 100 30 30 0 0 0 Wild oats. 100 90 100100 95 0 20 30 Chcatgrass. 100 60 100 100 90 0 20 O Foxtail A 100 100100 100 70 20 20 0 Barnyardgrass 100 90 100 100 70 0 50 0 Crabgrass 100100 100 100 95 0 90 0 Nutsedge 100 100 100 100 0 0 0 O J ohnsongrass 100100 100 100 20 0 20 0 Curled dock- 100 100 100 100 100 90 70 0 Snapbeans100 100 100 100 95 20 100 100 Chickwced 100 100 100 100 100 90 0 0 100100 100 100 0 30 4O 100 100 100 100 100 70 1 00 30 100 100 100 100 10080 1 00 80 100 100 100 100 100 100 95 100 100 100 100 100 100 1 00 0 i100 100 100 100 100 O 95 0 Percent control 3-(2-chloro-benzyl)3-(3-chloro-ben- 3-(4-ch1oro-bcn- 3-(3,4-dlchloro-3-(2,4-dichloropyrido[3,2-d] pyzyl)-pyrido (3,2-d] zyl)-pyrido[3,2-d]benzyl) -pyri lo benzg D-pyriqo rimldine-2,4(1H, pyrimidine-2,4pyrimidine 2,4 [3,2-d] pyrimi- [3,2- pyrimi- 3H)-diono (1H,3H)-dione(1H,3H)-dione dine-2,4(1H,3H)- dine-2,4(1H,3H)-

dione dione Pre Post Pro Post Pro Post Pre Post Pre Post 20 0 0 10 0 0 010 0 0 9O 10 0 3O 0 100 0 10 0 10 80 30 10 2O 0 30 0 20 0 20 40 20 50 100 0 0 10 0 0 80 0 20 20 0 0 O 20 0 10 100 0 90 O 0 0 0 10 0 10 0 0 O 0 00 0 0 0 Johnsongrass 30 10 3O 10 0 50 0 20 0 20 Curlcd dock 100 0 20 O60 0 0 0 0 Snapbeans... 90 10 40 10 0 90 0 10 20 40 Chickwecd. 100 100100 0 100 0 0 0 0 Cucumber. 10 20 0 30 20 40 0 30 20 30 PigwcctL 100 1000 50 0 100 0 0 40 Velvefleaf 0 0 0 7O 0 0 0 0 Lambsquarter. 100 90 100 O0 70 0 100 0 100 Mustard- 100 100 0 0 0 9O 0 30 0 0 Morning glo 0 0 0 0O 0 0 0 30 0 Percent control 344-methoxy- 3-[2-(2-pyridyl- 3-(3-pridylmethyl -pyrido 2,4(1H,3H)- dione 2,4(1H,3H)-dione 2,4(1 3H)-dionePrc Post Pre Post Pre Post 0 0 0 0 0 0 0 0 0 0 0 10 0 20 0 0 0 30 0 10 040 0 0 Barnyardgrass 0 10 O 0 0 10 Crabgrass V 0 0 0 0 0 10 N ntscdge Av 0 0 0 0 O 0 Jollnsongmss 0 1O 0 0 20 10 Chickwced c A 0 0 U 0 0 80 Cncnmbor 20 20 0 0 0 60 Pigwccd 0 30 O 0 0 100 Vclvctlcnf. 0 0 0 0 0 0Lnmbsquzn'tcrs 0 100 0 l) 20 100 Mustard c 0 0 0 100 0 100 Morning gloryTABLE IV Continued Percent control 3-tetrahydro-iur- 3-phenyl-pyridoB-piperidino- B-propar ld]pynm1dine2,4 2,4(1H,3H)-dionepyrimidinepyrimidine- (1H,3H)d1one 2,4(1B,3H) dione 2,4(1H,3H)-dione PrePost Pre Post Pre Post Pro 1 Post Corn 20 20 100 30 0 0 Wild oats v g 090 0 100 100 o o Cheatgrass 0 0 100 30 100 100 0 20 Foxtail a. U 0 90 40100 100 0 0 Barnyardgrass 70 0 95 60 100 95 0 0 Crahgrass... 95 10 100100 20 0 Nutscdge. A a 0 0 10 100 100 40 0 0 J'ohnsongrass. i A a 10 020 40 100 60 0 0 Curlcd dock. N 00 0 100 100 100 50 0 Snapbcans. a 100100 100 100 100 100 20 0 Chickweed 20 30 100 100 100 100 0 0 Cucumber:100 90 100 95 100 100 30 30 Pi d 50 50 100 100 100 100 50 0 velvetleaf95 100 1 0 100 100 100 0 o Lambsquarter 100 100 90 100 100 100 100 30Mustard i a 1 00 100 100 100 100 100 50 Morning glory 8 80 0 80 100 6030 80 1 Determined at 2 pounds per acre application rate.

Presented for purposes of comparison, and not in accordance with theinvention.

It will be appreciated from the foregoing data and discussion that thesubstituted pyrido[3,2- d]pyrimidine-2,4(lH,3H)-dione family ofcompounds described herein as unexpected utility as herbicides, and thatthis unexpected utility prevails throughout the family. For example, theshowing of a high order of herbicidal activity for C through C alkylsubstituents in the 3-position (3-substituted-pyrido[3,2-d]pyrimidine-2,4( lH,3l-l)-dione family) demonstrates the high order of activitywhere the 3-substituent is an alkyl group having from 2 to 8 carbonatoms. Furthermore, the demonstration that allyl, as a 3-substituent,has substantially the same order of activity as does an isopropylsubstituent in the 3 position shows that alkenyl substituents in thesame position impart activity of the same order as is imparted by alkylsubstituents and therefore, in view of the showing relative to suchalkyl substituents, demonstrates utility for 3 alkenyl substituentshaving not more than 8 carbon atoms. Further, the demonstration ofselectivity for a 3 benzyl substituent, as well as the showing of a highorder of activity therefor, demonstrates utility for aralkylsubstituents in the indicated position. When the substituent in the 3posi' tion is a pyridyl substituted alkyl group, the compounds of theinvention have somewhat lower activity, but are useful because of theirselectivity. The high order of activity of the compound where thesubstituent in the 3 position is piperidino, coupled with the showingrelative to alkyl substituents, demonstrates that the othermethyleneimino substituents (4 to 6 methylene groups) are also highlyactive.

Similarly the showing of the high order of herbicidal activity forl-methyl-3-isopropyl-pyrido[3,2- d]pyrimidine'2,4(1H,3l-l)-dione andessentially no activity for l,3-dimethyl-pyrido[ 3,2-d]pyrimidine-2,4(1H,3H)-dione demonstrates the high order of activity for thel,3-disubstituted compounds where the l and 3 substituents aredissimilar and where the 1 substituent is an alkyl group ranging from 1to 4 carbon atoms in length.

It has been found that, where the 3-substituent is a cycloalkyl group,the pyrido[3,2-d]pyrimidine- 2,4( lH,3H)-dione has a high order ofherbicidal activity when the cycloalkyl group has from 3 to 8 carbonatoms. When the cycloalkyl group has 12 carbon atoms, however, thepyrido[3,2-d]pyrimidine- 2,4( ll-l,3H)-dione is substantially inert as aherbicide. The herbicidal activity of 3-cycloalkyl pyrido[3,2-d]pyrimidine-2,4( lH,3H)-diones, where the cycloalkyl group has 9, 10 or11 carbon atoms has not presently been investigated, because thestarting amines required to produce such compounds by the methods ofExamples I and II are unavailable.

For practical use as herbicides, the compounds used in the method ofthis invention may be formulated with conventional agricultural carriersto obtain the desired concentration and to facilitate handling. Forexample, these compounds may be formulated into dusts by combining themwith such materials as talc or clays. Wettable powder formulations maybe obtained by adding a dispersing or suspending agent to the dustformulations referred to above.

If desired, the compounds may be applied as spray solutions which may beprepared by dissolving the compounds in suitable solvents, such aswater, xylene, methylated napththalenes, kerosenes, common agriculturaloils, etc., in accordance with well established agricultural practices.The choice of'solvent to be used will be dictated by the solubility ofthecompound sought to be sprayed in that particular solvent system.Generally, it has been found that the majority of these compounds have arelatively low order of water solubility, so that the use of commonagricultural organic solvents is the preferred practice.

The compounds of this invention may also be emulsified or suspended inwater by adding wetting agents or emulsifying agents to aqueous systemscontaining one or more of the chemical compounds falling under thisdisclosure. These emulsified formulations are suitable for use inspraying directly upon the locus sought to be protected from undesirablevegetation. So far as has been determined no significant difference ineffect is realized from the use of aqueous emulsified formulations orfrom organic solvent solutions of these herbicides, providing, ofcourse, that a similar amount of chemical is employed in each instanceof use.

If desired, the compounds can be converted to their salt forms, thendissolved in water and applied to water solutions. They can also beapplied as addition compounds and the like.

The alkali or alkaline earth metal and ammonium salts of the3-substituted pyrido[3,2- d]pyrimidine2,4(lH,3H)-diones can be preparedby the reaction of the dione with the desired metal hydroxide orammonium hydroxide.

Nitrogenous base addition compounds can be prepared by the addition ofthe desired nitrogenous base to a solution of the desired 3-substitutedpyrido [3,2-

d]pyrimidine-2,4( ll-l,3l-l)-dione in a suitable inert organic solvent.The addition compound can then be isolated by standard procedures.

Suitable nitrogenous bases are substituted, unsubstituted, cyclic andacylic amines and guanidines. The amines can be primary, secondary ortertiary amines, polyamines, arylamines, or heterocyclic amines.

Phenolic complexes are formed readily by co-melting the 3-substitutedpyrido[3,2-d]pyrimidine- 2,4(lH,3H)-dione and phenol in a 1:1 to 2:1,pyridopyrimidinedione: phenol ratio. They can also be formed byco-dissolving the reactants, in the same ratio in a nonpolar solventsuch as nitromethane or a mixture of nitromethane and cyclohexane.

Acid addition compounds can be prepared by mixing a 3-substitutedpyrido[3,2-d]pyrimidine-2,4(1H,3H)- dione with an appropriate acid, atroom temperature, in a liquid aromatic hydrocarbon solvent. The reactionis immediate. Generally any aromatic hydrocarbon can be used, but it ispreferred that it be liquid between 20 and 30. Benzene, toluene andxylene are examples of satisfactory solvents.

The acid addition compounds can be precipitated with an excess ofnon-solvent liquid paraffin such as pentane, hexane, heptane orpetroleum ether. The product precipitates as a solid or a viscous oilwhich can be separated by filtration or vacuum evaporation.Alternatively, the product can be separated by vacuum evaporation of thereaction medium at low temperatures, preferably below 50. Precipitationwith a nonsolvent is the usual method.

Most acids having an ionization constant greater than 2 X will form3-substituted pyrido[3,2- d]pyrimidine-2,4(1H,3H)-dione additioncompound. Preferred acids are halogenated aliphatic acids containingfrom 2 to 5 carbon atoms, halogenated benzoic acid, halogenatedphenylacetic acids, halogenated phenoxy acetic acids, organic sulfonicacids, organic phosphonic acids and inorganic phosphoric acids. Theseacids are preferred because the pyridopyrimidinedione addition compoundsformed from them are highly phytotoxic and show good oil solubility.

The preparation of various complexes, acid addition compounds and thelike is described in Examples B-F below:

EXAMPLE B Preparation of the 2:1 complex of 3-isopropyl-pyrido[ 3,2-d]pyrimidine-2,4( 1H,3 H)- dione with p-methoxyphenol A 50 ml. flask,equipped with a stirrer and heating mantle was charged with 7.5 g.3-isopropyl-pyrido [3,2- d]pyrimidine-2,4(1H,3l-l)-dione and 2 g.pmethoxyphenol. While being agitated, the reaction mixture was heated toa temperature of 180-200. It was maintained at 180200 for 2-5 minutes.The reaction mixture was then cooled, and solidified. The solid materialwas ground into a powder. The yield was 8.2 g. of the 2:1 complex of3-isopropyl-pyrido [3,2- d]pyrimidine-2,4(1H,3I-l)-dione withpmethoxyphenol having a melting point of l95-240.

EXAMPLE C Preparation of ethanolamine salt of3-isopropyl-pyrido[3,2-d]pyrimidine-2,4(1H,3H)-

dione A 50 ml. flask was charged with 5 g.3-isopropylpyrido[3,2d]pyrimidine-2,4(1H,3H)-dione and g.

ethanolamine. The mixture was allowed to stand for 24 hours, at whichtime a clear solution of the ethanolamine salt of3-isopropyl-pyrido[3,2-dlpyrimidine- 2,4(1H,3H)-dione formed.

EXAMPLE D Preparation of the ethylenediamine salt of 3-isopropyl-pyrido[3,2-d]pyrimidine-2,4( l l-l,3H)-

dione A 250 ml. 3-necked flask, equipped with a stirrer, droppingfunnel, and heating mantle was charged with 150 ml. acetonitrile and 5.1g. 3-isopropyl-pyrido[3,2- d]pyrimidine-2,4( lH,3H)-dione.

Agitation was begun and the mixture was heated to dissolve thecomponents and prepare a saturated solution. The solution was cooled toroom temperature and then charged with 1.5 g. ethylenediamine. Thereaction mixture was then stirred for 2 hours at room temperature. Theproduct which precipitated during this time was filtered from themixture and dried. The yield was 5.1 g. of product having a meltingpoint of 2525.

EXAMPLE E Preparation of a 1:1 complex of trichloroacetic acid with3-isopropyl-pyrido[3,2-d]pyrimidine-2,4( 111,311)- dione A 250 ml.3-necked flask equipped with a stirrer was charged with 5.1 g.3-isopropyl-pyrido[3,2- d]pyrimidine-2,4(1H,3H)-dione, 4.1 g.trichloroacetic acid, and 50 ml. xylene. The reaction mixture wasstirred for approximately 7 hours, at which time an additional 20 ml. ofxylene were added. The reaction mixture was stirred overnight. The nextmorning 150 ml. of n-hexane was charged to the reaction mixture withstirring. Stirring was continued and an hour later the mixture wasfiltered and a white solid recovered and dried. The yield was 9.4 g. ofproduct having a melting point of l50-1. Infrared analysis showed theformation of a complex, believed to be the 1:1 complex oftrichloroacetic acid and 3 isopropyl-pyrido[3,2-d]pyrimidine-2,4(1H,3l-l)-dione.

EXAMPLEF Preparation of the tetramethylammonium salt of3-isopropyl-pyrido[3,2-d]pyrimidine-2,4(1H,3H)-

dione A ml. 3-necked flask equipped with a stirrer, condenser,thermometer, and nitrogen atmosphere system was assembled. The nitrogenwas turned on and 5.5 g. tetramethylammonium chloride, 11.6 g. silveroxide, and 50.0 ml. water was charged to the flask. A brown thin slurryformed. The reaction mixture was filtered and the filtrate returned tothe flask. The temperature at this point was 25. 5.1 g.3-isopropylpyrido[3,2-d]pyrimidine-2,4(lH,3H)-dione was then charged tothe flask over a 10 minute period. The reaction mixture turned a lightyellow. V2 hour later another 5.1 g. portion of 3-isopropyl-pyrido[ 3.2- d]pyrimidine-2,4(1H,3H)-dione was charged, again over a ten minuteperiod. Some material failed to dis solve. After ten minutes it wasremoved by filtration and the filtrate was evaporated to dryness. Theresidue was dissolved in 10 ml. tap water, and the solution heated andthen filtered. The filtrate was again evaporated to dryness.

The yield was 14 g. of white material having a melting point of 164196.Nuclear magnetic resonance analysis confirmed the structure to be thatof the tetramethylammonium salt of 3-isopropyl[3,2-d1pyrido- 2,4(lH,3H)-dione, with one molecule of water in the structure.

The herbicidal activity of those compounds produced in Examples B-F wasfound to be substantially the same as the herbicidal activity of3-isopropyl-pyrido [3,2- d]pyrimidine-2,4(lH,3H)-dione, when applied atthe same active ingredient rate.

From the foregoing results it is apparent that the compounds fallingwithin the scope of this invention possess unexpected herbicidalproperties. Moreover, it has been shown that these compounds display ahigh rate of herbicidal activity while simultaneously demonstratingselectivity with respect to desirable, economic crops.

So far as concerns the amount of herbicide to be used this, of course,is subject to such considerations as the type of treatment to be made,the area to be treated, the type of weed sought to be controlled and thestage of development of the species being treated as well as theparticular herbicides selected. Generally, however, concentratedherbicidal compositions of the present invention are prepared so as tocontain from 5 to about 60 percent of the active herbicidal component.Compositions which are suitable for as is application generally containfrom 0.1 percent to about percent of active herbicidal component.

The 3substituted-pyrido[3,2-d] pyrimidine- 2,4(lH,3l-l)-diones accordingto the invention have also been found to be useful as aquaticherbicides, the compounds where the 3-substituent is a cycloaklyl groupbeing preferred for this use. Specifically, by way of example,3-cyclohexyl-pyrido[3,2-d] pyrimidine- 2,4(1H,3H)-dione and3-cyclooctyl-pyrido[3,2d] pyrimidine-2,4 (lH,3H)-dione have been foundto provide one hundred percent kill of duckweed, salvinia, and elodea inconcentrations of ten parts per million parts of water, while3-cycloheptyl-pyrido[3,2-d] pyrimidine-2,4 (ll-l,3H)-dione has beenfound to provide 100 percent kill of these three aquatic species in aconcentration of five parts per million parts of water,

by weight in both cases.

What we claim is:

l. A method of controlling plant growth comprising applying to the locusto be protected an effective amount of a compound having the formulawherein R and R are always dissimilar, wherein R is a member of thegroup consisting of alkyl groups having from 2 to 8 carbon atoms,dimethoxyethyl, aralkyl groups where the alkyl portion has from 1 to 2carbon atoms and the aromatic portion is phenyl or a substituted phenylhaving 1 or 2 methyl, methoxy or chlorine substituents on the benzenering, cycloalkyl groups having from 3 to 8 carbon atoms, pyridylsubstituted alkyl groups having from 1 to 2 carbon atoms, alkenyl groupshaving not more than 8 carbon atoms, tetrahydrofurfuryl, pyrrolidino,piperidino, homopiperidino, septamethyleneimino, and phenyl, and whereinR is hydrogen or a lower alkyl radical having from 1 to 4 carbon atoms.

2. The method of claim 1 wherein the compound is 3-sec-butyl-pyrido[3,2-d]pyrirnidine-2,4( lH,3H)- dione.

3. The method of claim 1 wherein the compound is3-allyl-pyrido-[3,2-d]pyrimidine-2,4( lH,3l-l)-dione.

4. The method of claim 1 wherein the compound is3-cycl0hexyl-pyrido[3,2-d]pyrimidine-2,4(1H,3H)- dione.

5. The method of claim 1 wherein the compound is3-benzyl-pyrido[3,2-d]pyrimidine-2,4( lH,3H )-dione.

6. The method of claim 1 wherein the compound is 3-isopropyl-pyridol3,2-d]pyrimidi:ne-2,4( 1H,3H)- dione.

7. The method of claim 1 wherein the compound isl-methyl-3-isopropyl-pyrido[ 3,2-d]pyrimidine- 8. The method of claim 1wherein the compound is 3-cyclooctyl-pyrido[ 3 ,2-d]pyrimidine-2,4(lH,3l-l dione.

9. The method of claim 1 wherein the compound is 3-cycloheptyl-pyrido[3,2-d]pyrimidine-2,4( lI-l,3H)- dione.

10. The method of claim 1 wherein the compound is 3-phenyl-pyrido[3,2-d]pyrimidine-2,4( lH,3H )-dione.

11. The method of claim 11 wherein R is hydrogen.

dione.

2. The method of claim 1 wherein the compound is3-sec-butyl-pyrido(3,2-d)pyrimidine-2,4(1H,3H)-dione.
 3. The method ofclaim 1 wherein the compound is3-allyl-pyrido-(3,2-d)pyrimidine-2,4(1H,3H)-dione.
 4. The method ofclaim 1 wherein the compound is3-cyclohexyl-pyrido(3,2-d)pyrimidine-2,4(1H,3H)-dione.
 5. The method ofclaim 1 wherein the compound is3-benzyl-pyrido(3,2-d)pyrimidine-2,4(1H,3H)-dione.
 6. The method ofclaim 1 wherein the compound is3-isopropyl-pyrido(3,2-d)pyrimidine-2,4(1H,3H)-dione.
 7. The method ofclaim 1 wherein the compound is1-methyl-3-isopropyl-pyrido(3,2-d)pyrimidine-2,4(1H,3H)-dione.
 8. Themethod of claim 1 wherein the compound is3-cyclooctyl-pyrido(3,2-d)pyrimidine-2,4(1H,3H)-dione.
 9. The method ofclaim 1 wherein the compound is3-cycloheptyl-pyrido(3,2-d)pyrimidine-2,4(1H,3H)-dione.
 10. The methodof claim 1 wherein the compound is3-phenyl-pyrido(3,2-d)pyrimidine-2,4(1H,3H)-dione.
 11. The method ofclaim 1 wherein R'' is hydrogen.
 12. The method of claim 1 wherein thecompound is 3-cyclopentyl-pyrido(3,2-d)pyrimidine-2,4(1H,3H)-dione.